The long term goal of this research is to learn how the primate brain comes to be assembled, so as to provide a basis for understanding and treating the diseases of the nervous system that arise before birth. Work on the embryonic and fetal brain directly in primates is essential for this purpose because some structures are poorly developed or do not even exist in lower mammals. Our effort is concentrated on analysis of the development of highly complex brain structures which have reached the peak of development in primates. The fetal brains are processed by several specialized cytological methods, including autoradiography, Golgi staining, electron microscopy and histochemistry. Particular attention is given to the interactions of brain cells as they multiply and change positions relative to one another at early stages of development and as post-migratory neurons develop their dendritic and axonal processes and establish synaptic connections that ultimately attain "wiring" arrangements of the mature brain. The projects currently under study concern: 1) a neuron-glia relationship during cell migration; 2) the kinetics of proliferation and latency between final cell division and onset of differentiation; 3) time of origin, mode of migration and pattern of distribution of neurons in the subcortical visual centers; 4) development of synaptic connections in the lateral geniculate body; 5) prenatal genesis of neuronal connections subserving binocular vision; 6) histogenesis of the hippocampal formation; 7) computer-aided three-dimensional reconstruction and quantitative analysis of cellular volume and surface area from serial electronmicroscopic images; 8) factors influencing the shape of neurons and their assembly into circuits; 9) gliogenesis, and 10) the adaptation and development of new methods for ontogenetic analyses. BIBLIOGRAPHIC REFERENCES: Zecevic, N. and Rakic, P. 1976 Differentiation of Purkinje cells and thier relationship to other components of developing cerebellar cortex in man. J. Comp. Neurol. (In press). Rakic, P. 1976b Synaptic specificity in the cerebellar cortex: Study of anomalous circuits induced by a single gene mutation in mice. In: The Synapse, Cold Spring Harbor Symposia on Quantitative Biology. 40: 333-346.